The aim of the proposed research project is the development of effective immunotherapy for colorectal cancer utilizing Immune RNA, an immunoreactive extract of lymphoid tissues. We propose to conduct clinical trials of immunotherapy with Immune RNA in two types of patients with adenocarcinomas of the colon and rectum. Patients entered into one study will have clinically demonstrable measurable disease and will be either 1) refractory to current therapy, 2) patients for whom no standard therapeutic modality of proven efficacy exists, or 3) patients with stable disease who can have standard therapy interrupted or the onset postponed for 8 weeks. Patients will be treated with xenogeneic Immune RNA extracted from the lymphoid organs of sheep immunized with autologous tumor tissue (whenever available) or with allogeneic tumor tissue of the same histogenic type. Immune RNA will be administered weekly intradermally at a dose of 4 mg/week for 8 weeks. Patients responding will be maintained at the same dose either 1) until relapse, 2) two years following disappearance of all detectable disease (complete response), or 3) indefinitely in the presence of a partial response following which stable disease continues. In the second study, adjuvant immunotherapy with Immune RNA will be given postoperatively to patients following complete resection of locally or regionally advanced colorectal carcinomas who fall in the category of "minimal residual disease" (i.e., greater than 50 percent likelihood of developing recurrence and/or metastases (within 24 months). These patients will receive 4 mg of Immune RNA intradermally weekly for 2 years or until recurrence and/or metastases are noted. The effects of treatment on a variety of immune parameters, both tumor specific and general (non-tumor specific) will be assessed in vitro and in vivo.